Skip to main content
Top
Published in: Infectious Diseases and Therapy 2/2024

Open Access 30-01-2024 | Clostridioides Difficile | Original Research

Association Between Risk of Clostridium difficile Infection and Duration of Proton Pump Inhibitor or H2-Receptor Antagonist Use in Hospitalized Patients

Authors: Chien-Huei Huang, Yung-Hsin Tseng, Wen-Shan Tsai, Chien-Chou Su, Ching-Lan Cheng, Yea-Huei Kao Yang, Yu-Ching Chang, Yi-Hsuan Liu

Published in: Infectious Diseases and Therapy | Issue 2/2024

Login to get access

Abstract

Introduction

Limited studies have evaluated the association between Clostridium difficile infection (CDI) and the duration of proton pump inhibitor (PPI) or histamine H2-receptor blocker (H2RA) use and provided a cutoff duration for PPI or H2RA use to mitigate a substantially increased risk of CDI. We aimed to evaluate these associations in hospitalized patients using a nationwide insurance claims database.

Methods

We conducted a nested case–control study to identify cases with a first ever record of CDI in a study cohort undergoing PPI or H2RA therapy from the National Health Insurance Database from 2012 to 2018. Each case was matched with one control by age, sex, and calendar year. We used conditional logistic regression to estimate the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC ROC). Youden’s J statistic was used to identify the optimal cutoff duration in days for PPI or H2RA use.

Results

In the main analysis, the AUC ROC was 0.64 (95% CI 0.63–0.66) and optimal cutoff duration was 15 days for PPI users. The AUC ROC was 0.63 (95% CI 0.62–0.64) and optimal cutoff duration was 16 days for H2RA users. In the sensitivity analyses, the results were similar to those of the main analysis, and the optimal cutoff duration was in the range of 14–15 days.

Conclusions

The optimal cutoff duration for PPI and H2RA use was about 2 weeks. It is necessary to be cautious regarding the risk of CDI in patients taking PPIs or H2RAs for longer than 2 weeks.
Appendix
Available only for authorised users
Literature
1.
go back to reference Ramaswamy R, Grover H, Corpuz M, Daniels P, Pikhumoni C. Prognostic criteria in Clostridium difficile colitis. Am J Gastroenterol. 1996;91(3):460–4. Ramaswamy R, Grover H, Corpuz M, Daniels P, Pikhumoni C. Prognostic criteria in Clostridium difficile colitis. Am J Gastroenterol. 1996;91(3):460–4.
2.
go back to reference Kyne L, Hamel MB, Polavaram R, Kelly CP. Health care costs and mortality associated with nosocomial diarrhea due to Clostridium difficile. Clin Infect Dis. 2002;34(3):346–53.CrossRefPubMed Kyne L, Hamel MB, Polavaram R, Kelly CP. Health care costs and mortality associated with nosocomial diarrhea due to Clostridium difficile. Clin Infect Dis. 2002;34(3):346–53.CrossRefPubMed
3.
go back to reference Kenneally C, Rosini JM, Skrupky LP, et al. Analysis of 30-day mortality for Clostridium difficile-associated disease in the icu setting. Chest. 2007;132(2):418–24.CrossRefPubMed Kenneally C, Rosini JM, Skrupky LP, et al. Analysis of 30-day mortality for Clostridium difficile-associated disease in the icu setting. Chest. 2007;132(2):418–24.CrossRefPubMed
5.
go back to reference Shrestha A, Kalapurayil M, Bailey J, Deol H, Singh R, Surani S. Examining risk of C difficile infection with use of proton pump inhibitor vs H2 receptor antagonist. Chest. 2018;154(4):374A.CrossRef Shrestha A, Kalapurayil M, Bailey J, Deol H, Singh R, Surani S. Examining risk of C difficile infection with use of proton pump inhibitor vs H2 receptor antagonist. Chest. 2018;154(4):374A.CrossRef
7.
8.
go back to reference Tariq R, Singh S, Gupta A, Pardi DS, Khanna S. Association of gastric acid suppression with recurrent Clostridium difficile infection: a systematic review and meta-analysis. JAMA Intern Med. 2017;177(6):784–91.CrossRefPubMedPubMedCentral Tariq R, Singh S, Gupta A, Pardi DS, Khanna S. Association of gastric acid suppression with recurrent Clostridium difficile infection: a systematic review and meta-analysis. JAMA Intern Med. 2017;177(6):784–91.CrossRefPubMedPubMedCentral
9.
go back to reference Al-Aly Z, Maddukuri G, Xie Y. Proton pump inhibitors and the kidney: implications of current evidence for clinical practice and when and how to deprescribe. Am J Kidney Dis. 2020;75(4):497–507.CrossRefPubMed Al-Aly Z, Maddukuri G, Xie Y. Proton pump inhibitors and the kidney: implications of current evidence for clinical practice and when and how to deprescribe. Am J Kidney Dis. 2020;75(4):497–507.CrossRefPubMed
11.
go back to reference Trifan A, Stanciu C, Girleanu I, et al. Proton pump inhibitors therapy and risk of Clostridium difficile infection: systematic review and meta-analysis. World J Gastroenterol. 2017;23(35):6500–15.CrossRefPubMedPubMedCentral Trifan A, Stanciu C, Girleanu I, et al. Proton pump inhibitors therapy and risk of Clostridium difficile infection: systematic review and meta-analysis. World J Gastroenterol. 2017;23(35):6500–15.CrossRefPubMedPubMedCentral
12.
go back to reference Seo SI, You SC, Park CH, et al. Comparative risk of Clostridium difficile infection between proton pump inhibitors and histamine-2 receptor antagonists: a 15-year hospital cohort study using a common data model. J Gastroenterol Hepatol. 2020;35(8):1325–30.CrossRefPubMed Seo SI, You SC, Park CH, et al. Comparative risk of Clostridium difficile infection between proton pump inhibitors and histamine-2 receptor antagonists: a 15-year hospital cohort study using a common data model. J Gastroenterol Hepatol. 2020;35(8):1325–30.CrossRefPubMed
13.
15.
go back to reference Sundararajan V, Henderson T, Perry C, Muggivan A, Quan H, Ghali WA. New ICD-10 version of the Charlson comorbidity index predicted in-hospital mortality. J Clin Epidemiol. 2004;57(12):1288–94.CrossRefPubMed Sundararajan V, Henderson T, Perry C, Muggivan A, Quan H, Ghali WA. New ICD-10 version of the Charlson comorbidity index predicted in-hospital mortality. J Clin Epidemiol. 2004;57(12):1288–94.CrossRefPubMed
16.
go back to reference Kimura T, Stanhope S, Sugitani T. Clostridioides (Clostridium) difficile infection in Japanese hospitals 2008–2017: a real-world nationwide analysis of treatment pattern, incidence and testing density. J Infect Chemother. 2020;26(5):438–43.CrossRefPubMed Kimura T, Stanhope S, Sugitani T. Clostridioides (Clostridium) difficile infection in Japanese hospitals 2008–2017: a real-world nationwide analysis of treatment pattern, incidence and testing density. J Infect Chemother. 2020;26(5):438–43.CrossRefPubMed
17.
go back to reference Azab M, Doo L, Doo DH, et al. Comparison of the hospital-acquired Clostridium difficile infection risk of using proton pump inhibitors versus histamine-2 receptor antagonists for prophylaxis and treatment of stress ulcers: a systematic review and meta-analysis. Gut liver. 2017;11(6):781–8.CrossRefPubMedPubMedCentral Azab M, Doo L, Doo DH, et al. Comparison of the hospital-acquired Clostridium difficile infection risk of using proton pump inhibitors versus histamine-2 receptor antagonists for prophylaxis and treatment of stress ulcers: a systematic review and meta-analysis. Gut liver. 2017;11(6):781–8.CrossRefPubMedPubMedCentral
19.
go back to reference Berbudi A, Rahmadika N, Tjahjadi AI, Ruslami R. Type 2 diabetes and its impact on the immune system. Curr Diabetes Rev. 2020;16(5):442–9.PubMedPubMedCentral Berbudi A, Rahmadika N, Tjahjadi AI, Ruslami R. Type 2 diabetes and its impact on the immune system. Curr Diabetes Rev. 2020;16(5):442–9.PubMedPubMedCentral
20.
go back to reference Leonard J, Marshall JK, Moayyedi P. Systematic review of the risk of enteric infection in patients taking acid suppression. Am J Gastroenterol. 2007;102(9):2047–56.CrossRefPubMed Leonard J, Marshall JK, Moayyedi P. Systematic review of the risk of enteric infection in patients taking acid suppression. Am J Gastroenterol. 2007;102(9):2047–56.CrossRefPubMed
21.
go back to reference Romero R, Hassan SS, Gajer P, et al. The composition and stability of the vaginal microbiota of normal pregnant women is different from that of non-pregnant women. Microbiome. 2014;2(1):4.CrossRefPubMedPubMedCentral Romero R, Hassan SS, Gajer P, et al. The composition and stability of the vaginal microbiota of normal pregnant women is different from that of non-pregnant women. Microbiome. 2014;2(1):4.CrossRefPubMedPubMedCentral
22.
go back to reference Tawam D, Baladi M, Jungsuwadee P, Earl G, Han J. The positive association between proton pump inhibitors and Clostridium difficile infection. Innov Pharm. 2021;12(1):10.24926 Tawam D, Baladi M, Jungsuwadee P, Earl G, Han J. The positive association between proton pump inhibitors and Clostridium difficile infection. Innov Pharm. 2021;12(1):10.24926
23.
go back to reference Herszényi L, Bakucz T, Barabás L, Tulassay Z. Pharmacological approach to gastric acid suppression: past, present, and future. Dig Dis. 2020;38(2):104–11.CrossRefPubMed Herszényi L, Bakucz T, Barabás L, Tulassay Z. Pharmacological approach to gastric acid suppression: past, present, and future. Dig Dis. 2020;38(2):104–11.CrossRefPubMed
24.
go back to reference Howell MD, Novack V, Grgurich P, et al. Iatrogenic gastric acid suppression and the risk of nosocomial Clostridium difficile infection. Arch Intern Med. 2010;170(9):784–90.CrossRefPubMed Howell MD, Novack V, Grgurich P, et al. Iatrogenic gastric acid suppression and the risk of nosocomial Clostridium difficile infection. Arch Intern Med. 2010;170(9):784–90.CrossRefPubMed
26.
go back to reference D’Silva KM, Mehta R, Mitchell M, et al. Proton pump inhibitor use and risk for recurrent clostridioides difficile infection: a systematic review and meta-analysis. Clin Microbiol Infect. 2021;27(5):697–703.CrossRef D’Silva KM, Mehta R, Mitchell M, et al. Proton pump inhibitor use and risk for recurrent clostridioides difficile infection: a systematic review and meta-analysis. Clin Microbiol Infect. 2021;27(5):697–703.CrossRef
Metadata
Title
Association Between Risk of Clostridium difficile Infection and Duration of Proton Pump Inhibitor or H2-Receptor Antagonist Use in Hospitalized Patients
Authors
Chien-Huei Huang
Yung-Hsin Tseng
Wen-Shan Tsai
Chien-Chou Su
Ching-Lan Cheng
Yea-Huei Kao Yang
Yu-Ching Chang
Yi-Hsuan Liu
Publication date
30-01-2024
Publisher
Springer Healthcare
Published in
Infectious Diseases and Therapy / Issue 2/2024
Print ISSN: 2193-8229
Electronic ISSN: 2193-6382
DOI
https://doi.org/10.1007/s40121-024-00922-5

Other articles of this Issue 2/2024

Infectious Diseases and Therapy 2/2024 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine